RESUMEN
BACKGROUND: Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. METHODS: This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. RESULTS: CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. CONCLUSIONS: In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features.
Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Transición Epitelial-Mesenquimal , Células Neoplásicas Circulantes/patología , Proteínas Nucleares/genética , Factores de Transcripción/genética , Proteína 1 Relacionada con Twist/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HeLa , Humanos , Células MCF-7 , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Factores de Transcripción de la Familia Snail , Factores de Transcripción/metabolismo , Proteína 1 Relacionada con Twist/metabolismoRESUMEN
The authors describe a case of recurrent malignant epitheloid schwannoma of the lower lip. Histologically, the tumor was composed of fibroblast-like spindle cells in compact fascicles and areas of epitheloid growth, combined with demonstration of S-100, GFAP and NF positivity, which is characteristic for this type of tumor. The therapy consisted of a combination of surgery and radiotherapy and the patient was followed-up since the disease was diagnosed. A local re-operation had to follow the first surgical intervention consisting of a radical excision of tumor in the lower lip together with suprahyoid neck dissection six months later. After the first operation, the patient received a radiation therapy with a total dosage of 12 Gy in seven fractions to the tumor area of the lower lip. After the second operation, an external radiotherapy with total dosage of 50 Gy was applied. Despite the complex intensive therapy, the patient died of metastases into lungs, liver and spine 37 months after the initiation of the therapy (Fig. 2, Ref. 17). Full Text (Free, PDF) www.bmj.sk.